Selective Chemical Inhibition of PGC-1α Gluconeogenic Activity Ameliorates Type 2 Diabetes.

Type 2 diabetes (T2D) is a worldwide epidemic with a medical need for additional targeted therapies. Suppression of hepatic glucose production (HGP) effectively ameliorates diabetes and can be exploited for its treatment. We hypothesized that targeting PGC-1α acetylation in the liver, a chemical modification known to inhibit hepatic gluconeogenesis, could be potentially used for treatment of T2D. Thus, we designed a high-throughput chemical screen platform to quantify PGC-1α acetylation in cells and identified small molecules that increase PGC-1α acetylation, suppress gluconeogenic gene expression, and reduce glucose production in hepatocytes. On the basis of potency and bioavailability, we selected a small molecule, SR-18292, that reduces blood glucose, strongly increases hepatic insulin sensitivity, and improves glucose homeostasis in dietary and genetic mouse models of T2D. These studies have important implications for understanding the regulatory mechanisms of glucose metabolism and treatment of T2D.

The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of Mitochondria.

Brown and beige adipocytes are specialized cells that express uncoupling protein 1 (UCP1) and dissipate chemical energy as heat. These cells likely possess alternative UCP1-independent thermogenic mechanisms. Here, we identify a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that is enriched in UCP1(+) versus UCP1(-) adipocytes. We demonstrate that PM20D1 is a bidirectional enzyme in vitro, catalyzing both the condensation of fatty acids and amino acids to generate N-acyl amino acids and also the reverse hydrolytic reaction. N-acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. Mice with increased circulating PM20D1 have augmented respiration and increased N-acyl amino acids in blood. Lastly, administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure. These data identify an enzymatic node and a family of metabolites that regulate energy homeostasis. This pathway might be useful for treating obesity and associated disorders.

Pancreatic ß cell dedifferentiation as a mechanism of diabetic ß cell failure.

Diabetes is associated with ß cell failure. But it remains unclear whether the latter results from reduced ß cell number or function. FoxO1 integrates ß cell proliferation with adaptive ß cell function. We interrogated the contribution of these two processes to ß cell dysfunction, using mice lacking FoxO1 in ß cells. FoxO1 ablation caused hyperglycemia with reduced ß cell mass following physiologic stress, such as multiparity and aging. Surprisingly, lineage-tracing experiments demonstrated that loss of ß cell mass was due to ß cell dedifferentiation, not death. Dedifferentiated ß cells reverted to progenitor-like cells expressing Neurogenin3, Oct4, Nanog, and L-Myc. A subset of FoxO1-deficient ß cells adopted the α cell fate, resulting in hyperglucagonemia. Strikingly, we identify the same sequence of events as a feature of different models of murine diabetes. We propose that dedifferentiation trumps endocrine cell death in the natural history of ß cell failure and suggest that treatment of ß cell dysfunction should restore differentiation, rather than promoting ß cell replication.

Integrative multiomics profiling of passion fruit reveals the genetic basis for fruit color and aroma.

Passion fruit (Passiflora edulis) possesses a complex aroma and is widely grown in tropical and subtropical areas. Here, we conducted the de novo assembly, annotation, and comparison of PPF (P. edulis Sims) and YPF (P. edulis f. flavicarpa) reference genomes using PacBio, Illumina, and Hi-C technologies. Notably, we discovered evidence of recent whole-genome duplication events in P. edulis genomes. Comparative analysis revealed 7.6∼8.1 million single nucleotide polymorphisms, 1 million insertions/deletions, and over 142 Mb presence/absence variations among different P. edulis genomes. During the ripening of yellow passion fruit, metabolites related to flavor, aroma, and color were substantially accumulated or changed. Through joint analysis of genomic variations, differentially expressed genes, and accumulated metabolites, we explored candidate genes associated with flavor, aroma, and color distinctions. Flavonoid biosynthesis pathways, anthocyanin biosynthesis pathways, and related metabolites are pivotal factors affecting the coloration of passion fruit, and terpenoid metabolites accumulated more in PPF. Finally, by heterologous expression in yeast (Saccharomyces cerevisiae), we functionally characterized 12 terpene synthases. Our findings revealed that certain TPS homologs in both YPF and PPF varieties produce identical terpene products, while others yield distinct compounds or even lose their functionality. These discoveries revealed the genetic and metabolic basis of unique characteristics in aroma and flavor between the 2 passion fruit varieties. This study provides resources for better understanding the genome architecture and accelerating genetic improvement of passion fruits.

Effects of accelerated intermittent theta-burst stimulation in modulating brain of Alzheimer's disease.

Intermittent theta-burst stimulation (iTBS) is emerging as a noninvasive therapeutic strategy for Alzheimer's disease (AD). Recent advances highlighted a new accelerated iTBS (aiTBS) protocol, consisting of multiple sessions per day and higher overall pulse doses, in brain modulation. To examine the possibility of applying the aiTBS in treating AD patients, we enrolled 45 patients in AD at early clinical stages, and they were randomly assigned to either receive real or sham aiTBS. Neuropsychological scores were evaluated before and after treatment. Moreover, we detected cortical excitability and oscillatory activity changes in AD, by the single-pulse TMS in combination with EEG (TMS-EEG). Real stimulation showed markedly better performances in the group average of Auditory Verbal Learning Test scores compared to baseline. TMS-EEG revealed that aiTBS has reinforced this memory-related cortical mechanism by increasing cortical excitability and beta oscillatory activity underlying TMS target. We also found an enhancement of local natural frequency after aiTBS treatment. The novel findings implicated that high-dose aiTBS targeting left DLPFC is rapid-acting, safe, and tolerable in AD patients. Furthermore, TMS-related increase of specific neural oscillation elucidates the mechanisms of the AD cognitive impairment ameliorated by aiTBS.

rTMS concurrent with cognitive training rewires AD brain by enhancing GM-WM functional connectivity: a preliminary study.

Repetitive transcranial magnetic stimulation (rTMS) and cognitive training for patients with Alzheimer's disease (AD) can change functional connectivity (FC) within gray matter (GM). However, the role of white matter (WM) and changes of GM-WM FC under these therapies are still unclear. To clarify this problem, we applied 40 Hz rTMS over angular gyrus (AG) concurrent with cognitive training to 15 mild-moderate AD patients and analyzed the resting-state functional magnetic resonance imaging before and after treatment. Through AG-based FC analysis, corona radiata and superior longitudinal fasciculus (SLF) were identified as activated WM tracts. Compared with the GM results with AG as seed, more GM regions were found with activated WM tracts as seeds. The averaged FC, fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) of the above GM regions had stronger clinical correlations (r/P = 0.363/0.048 vs 0.299/0.108, 0.351/0.057 vs 0.267/0.153, 0.420/0.021 vs 0.408/0.025, for FC/fALFF/ReHo, respectively) and better classification performance to distinguish pre-/post-treatment groups (AUC = 0.91 vs 0.88, 0.65 vs 0.63, 0.87 vs 0.82, for FC/fALFF/ReHo, respectively). Our results indicated that rTMS concurrent with cognitive training could rewire brain network by enhancing GM-WM FC in AD, and corona radiata and SLF played an important role in this process.

DNA damage reduces heterogeneity and coherence of chromatin motions.

Chromatin motions depend on and may regulate genome functions, in particular the DNA damage response. In yeast, DNA double-strand breaks (DSBs) globally increase chromatin diffusion, whereas in higher eukaryotes the impact of DSBs on chromatin dynamics is more nuanced. We mapped the motions of chromatin microdomains in mammalian cells using diffractive optics and photoactivatable chromatin probes and found a high level of spatial heterogeneity. DNA damage reduces heterogeneity and imposes spatially defined shifts in motions: Distal to DNA breaks, chromatin motions are globally reduced, whereas chromatin retains higher mobility at break sites. These effects are driven by context-dependent changes in chromatin compaction. Photoactivated lattices of chromatin microdomains are ideal to quantify microscale coupling of chromatin motion. We measured correlation distances up to 2 µm in the cell nucleus, spanning chromosome territories, and speculate that this correlation distance between chromatin microdomains corresponds to the physical separation of A and B compartments identified in chromosome conformation capture experiments. After DNA damage, chromatin motions become less correlated, a phenomenon driven by phase separation at DSBs. Our data indicate tight spatial control of chromatin motions after genomic insults, which may facilitate repair at the break sites and prevent deleterious contacts of DSBs, thereby reducing the risk of genomic rearrangements.

Breaking Through the Trade-Off Between Wide Band Gap and Large SHG Coefficient in Mercury-Based Chalcogenides for IR Nonlinear Optical Application.

It is substantially challenging for non-centrosymmetric (NCS) Hg-based chalcogenides for infrared nonlinear optical (IR-NLO) applications to realize wide band gap (Eg > 3.0 eV) and sufficient phase-matching (PM) second-harmonic-generation intensity (deff > 1.0 × benchmark AgGaS2 ) simultaneously due to the inherent incompatibility. To address this issue, this work presents a diagonal synergetic substitution strategy for creating two new NCS quaternary Hg-based chalcogenides, AEHgGeS4 (AE = Sr and Ba), based on the centrosymmetric (CS) AEIn2 S4 . The derived AEHgGeS4 displays excellent NLO properties such as a wide Eg (≈3.04-3.07 eV), large PM deff (≈2.2-3.0 × AgGaS2 ), ultra-high laser-induced damage threshold (≈14.8-15 × AgGaS2 ), and suitable Δn (≈0.19-0.24@2050 nm), making them highly promising candidates for IR-NLO applications. Importantly, such excellent second-order NLO properties are primarily attributed to the synergistic combination of tetrahedral [HgS4 ] and [GeS4 ] functional primitives, as supported by detailed theoretical calculations. This study reports the first two NCS Hg-based materials with well-balanced comprehensive properties (i.e., Eg > 3.0 eV and deff > 1.0 × benchmark AgGaS2 ) and puts forward a new design avenue for the construction of more efficient IR-NLO candidates.

pH-Responsive Amphiphilic Triblock Fluoropolymers as Assemble Oxygen Nanoshuttles for Enhancing PDT against Hypoxic Tumor.

Photodynamic therapy (PDT) is a cancer treatment strategy that utilizes photosensitizers to convert oxygen within tumors into reactive singlet oxygen (1O2) to lyse tumor cells. Nevertheless, pre-existing tumor hypoxia and oxygen consumption during PDT can lead to an insufficient oxygen supply, potentially reducing the photodynamic efficacy. In response to this issue, we have devised a pH-responsive amphiphilic triblock fluorinated polymer (PDP) using copper-mediated RDRP. This polymer, composed of poly(ethylene glycol) methyl ether acrylate, 2-(diethylamino)ethyl methacrylate, and (perfluorooctyl)ethyl acrylate, self-assembles in an aqueous environment. Oxygen, chlorine e6 (Ce6), and doxorubicin (DOX) can be codelivered efficiently by PDP. The incorporation of perfluorocarbon into the formulation enhances the oxygen-carrying capacity of PDP, consequently extending the lifetime of 1O2. This increased lifetime, in turn, amplifies the PDT effect and escalates the cellular cytotoxicity. Compared with PDT alone, PDP@Ce6-DOX-O2 NPs demonstrated significant inhibition of tumor growth. This study proposes a novel strategy for enhancing the efficacy of PDT.

Utility of MRI-based vertebral bone quality scores and CT-based Hounsfield unit values in vertebral bone mineral density assessment for patients with diffuse idiopathic skeletal hyperostosis.

This study investigated bone mineral density assessment for patients with DISH. DXA-based T-scores overestimated bone quality, while MRI-based VBQ scores and CT-based HU values provided accurate assessments, particularly for advanced degenerative cases. This enhances accurate evaluation of BMD, crucial for clinical decision-making. PURPOSE: To investigate the diagnostic effectiveness of DXA, MRI, and CT in assessing bone mineral density (BMD) for diffuse idiopathic skeletal hyperostosis (DISH) patients. METHODS: Retrospective analysis of 105 DISH patients and 116 age-matched controls with lumbar spinal stenosis was conducted. BMD was evaluated using DXA-based T-scores, MRI-based vertebral bone quality (VBQ) scores, and CT-based Hounsfield unit (HU) values. Patients were categorized into three BMD subgroups. Lumbar osteophyte categories were determined by Mata score. Demographics, clinical data, T-scores, VBQ scores, and HU values were collected. Receiver operating characteristic (ROC) analysis identified VBQ and HU thresholds for diagnosing normal BMD using DXA in controls. Correlations between VBQ, HU, and lumbar T-score were analyzed. RESULTS: Age, gender, and BMI showed no significant differences between DISH and control groups. DISH patients had higher T-score (L1-4), the lowest T-score, and Mata scores. VBQ and HU did not significantly differ between groups. In controls, VBQ and HU effectively diagnosed normal BMD (AUC = 0.857 and 0.910, respectively) with cutoffs of 3.0 for VBQ and 104.3 for HU. DISH had higher normal BMD prevalence using T-scores (69.5% vs. 58.6%, P < 0.05), but no significant differences using VBQ (57.1% vs. 56.2%, P > 0.05) and HU (58.1% vs. 57.8%, P > 0.05). Correlations revealed moderate correlations between HU and T-scores (L1-4) in DISH (r = 0.642, P < 0.001) and strong in controls (r = 0.846, P < 0.001). Moderate negative correlations were observed between VBQ and T-scores (L1-4) in DISH (r = - 0.450, P < 0.001) and strong in controls (r = - 0.813, P < 0.001). CONCLUSION: DXA-based T-scores may overestimate BMD in DISH. VBQ scores and HU values could effectively complement BMD assessment, particularly in DISH patients or those with advanced lumbar degeneration.

Clinical characteristics and prognosis of patients with newly diagnosed primary central nervous system lymphoma: a multicentre retrospective analysis.

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

Ba10In2Mn11Si3O12S18: First Hexanary Oxychalcogenide Containing an Infrequent Three-Dimensional Noncentrosysmmetric Framework.

Noncentrosymmetric (NCS) oxychalcogenides have attracted great attention in recent years due to their immense potential as candidates for IR nonlinear-optical (NLO) applications. Despite notable advancements in this field, the discovery of oxychalcogenides with three-dimensional (3D) framework structures remains a formidable challenge. In this study, we report the discovery of the first hexanary oxychalcogenide, Ba10In2Mn11Si3O12S18, exhibiting second-order NLO activity, using a high-temperature solid-phase method. This compound showcases a novel structure type, featuring an uncommon NCS 3D [In2Mn11Si3O12S18]20- framework formed by vertex-sharing [(Mn/In)S6] octahedra, [(Mn/In)OS3] tetrahedra, and [SiO4] tetrahedra, with charge-balanced Ba2+ cations occupying the channels. Our study serves as a source of inspiration for researchers to further investigate the synthesis of novel NLO-active oxychalcogenides with 3D frameworks.

Rare-Earth Metal-Organic Framework with Nonplanar Porphyrin Groups for High-Efficiency Photocatalysis.

Nonplanar porphyrins play crucial roles in many biological processes and chemical reactions as catalysts. However, the preparation of artificial nonplanar porphyrins suffers from complicated organic syntheses. Herein, we present a new rare-earth porphyrinic metal-organic framework (RE-PMOF), BUT-233, which is a three-dimensional (3D) framework structure with the flu topology consisting of 4-connected BBCPPP-Ph ligands H4BBCPPP-Ph = 5',5⁗-(10,20-diphenylporphyrin-5,15-diyl)bis([1,1':3',1″-terphenyl]-4,4'' dicarboxylic acid) and 8-connected Eu6 clusters. Noteworthily, the porphyrin cores of the BBCPPP-Ph ligands in BUT-233 are nonplanar with a ruffle-like conformation. In contrast, the porphyrin core in the free ligand H4BBCPPP-Ph is in a nearly ideally planar conformation, as confirmed by its single-crystal structure. BUT-233 is microporous with 6-8 Špores and a Brunauer-Emmett-Teller (BET) surface area of 649 m2/g, as well as high stability in common solvents. The MOF was used as a photocatalyst for the oxidation degradation of a chemical warfare agent model molecule CEES (CEES = 2-chloroethyl ethyl sulfide) under the light-emitting diode (LED) irradiation and an O2 atmosphere at room temperature. CEES was almost completely converted into its nontoxic light-oxidized product CEESO (CEESO = 2-chloroethyl ethyl sulfoxide) in only 5 min with t1/2 = 2 min (t1/2: half-life). Moreover, the toxic deep-oxidized product 2-chloroethyl ethyl sulfone (CEESO2) was not detected. The catalytic activity of BUT-233 was high in comparison with those of some previously reported MOF catalysts. The results of photo/electrochemical property studies suggested that the high catalytic activity of BUT-233 was benefited from the presence of nonplanar porphyrin rings on its pore surface.

Interior and Exterior Surface Modification of Zr-Based Metal-Organic Frameworks for Trace Benzene Removal.

The emission of volatile organic compounds (VOCs) significantly contributes to air pollution and poses a serious threat to human health. Benzene, one of the most toxic VOCs, is difficult for the human body to metabolize and is classified as a Group 1 carcinogen. The development of efficient adsorbents for removing trace amounts of benzene from ambient air is thus of great importance. In this work, we studied the benzene adsorption properties of four Zr-based metal-organic frameworks (Zr-MOFs) through static volumetric and dynamic breakthrough experiments. Two previously reported Zr-MOFs, BUT-12 and STA-26, were prepared with a tritopic carboxylic acid ligand (H3L1) functionalized with three methyl groups, and STA-26 is a 2-fold interpenetrated network of BUT-12. Two new isoreticular Zr-MOFs, BUT-12-Et and STA-26-Et, were synthesized using a similar ligand, H3L2, where the methyl groups are replaced with ethyl groups. There are mesopores in BUT-12 and BUT-12-Et and micropores in STA-26 and STA-26-Et. The four Zr-MOFs all showed high stability in liquid water and acidic aqueous solutions. The microporous STA-26 and STA-26-Et showed much higher benzene uptakes than mesoporous BUT-12 and BUT-12-Et at room temperature under low pressures. Particularly, the benzene adsorption capacity of STA-26-Et was high up to 2.21 mmol/g at P/P0 = 0.001 (P0 = 12.78 kPa), higher than those of the other three Zr-MOFs and most reported solid adsorbents. Breakthrough experiments confirmed that STA-26-Et could effectively capture trace benzene (10 ppm) from dry air; however, its benzene capture capacity was reduced by 90% under humid conditions (RH = 50%). Coating of the crystals of STA-26-Et with polydimethylsiloxane (PDMS) increased the hydrophobicity of the exterior MOF surfaces, leading to a more than 2-fold improvement in its benzene capture capacity in the breakthrough experiment under humid condition. PDMS coating of STA-26-Et likely slowed down the water adsorption process, and thus, the adsorbent afforded more efficient capture of benzene. This work demonstrates that modifying both the interior and exterior surfaces of MOFs can effectively enhance their performance in capturing trace benzene from ambient air, even under humid conditions. This finding is meaningful for the development of new adsorbents for effective air purification applications.

Characteristics of reproductive tract infections caused by common pathogens among the outpatients of reproductive medicine center in Putian: retrospective study.

BACKGROUND: This study aims to explore the infection and age distribution of Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Herpes simplex virus type II (HSV II) among the outpatients of Reproductive Medicine Center in Putian, Fujian Province to provide a clinical basis for the early diagnosis and treatment of various reproductive tract diseases and infertility in this region. METHODS: A total of 1736 samples of secretions and exfoliated cervical cells were collected from the outpatients of the Reproductive Medicine Center of the Affiliated Hospital of Putian University from December 2021 to April 2023. The infections of UU, CT, NG and HSVII were detected by real-time fluorescence polymerase chain reaction (PCR), and the infection statuses of the patients with different genders, ages and diagnoses were analysed. RESULTS: Among the 1736 patients, 611 were male and 1125 were female. The male patients had higher UU infection rate but lower HSV II infection rate than the female patients. No significant difference in CT and NG infection rates was observed between the genders. The CT infection rate gradually decreased with the increase in the age. The difference in UU, NG and HSV II infection rates among the different age groups was not statistically significant. For UU infection, the male infertile patients had the highest rate of 37.72% (172/456). Meanwhile, the differences in CT, NG and HSV II infection rates among the different diagnosis groups were not statistically significant. Among the male and female infertile patients, the CT infection rate was the highest in the 21-25 years of age group at 11.11% (2/18) and 9.47% (9/95), respectively. No statistically significant difference in UU, CT, NG and HSV II infection rates was observed among the different age groups of patients diagnosed in relation to the family planning guidance and between the male and female patients with other diagnoses results. CONCLUSIONS: This study showed that UU was the most frequently identified pathogen in infertile men in Putian, Fujian Province. The CT infection rate was the highest in people under 20 years old, and the infection showed a tendency toward young individuals. Therefore, the publicity of sexual health knowledge must be strengthened, and the prevention and treatment of venereal diseases among young and middle-aged people must be improved. Moreover, the pathogen infection is related to infertility to a certain extent, which is conducive to clinical diagnosis and treatment.

Identification of subjective cognitive decline due to Alzheimer's disease using multimodal MRI combining with machine learning.

Subjective cognitive decline (SCD) is a preclinical asymptomatic stage of Alzheimer's disease (AD). Accurate diagnosis of SCD represents the greatest challenge for current clinical practice. The multimodal magnetic resonance imaging (MRI) features of 7 brain networks and 90 regions of interests from Chinese and ANDI cohorts were calculated. Machine learning (ML) methods based on support vector machine (SVM) were used to classify SCD plus and normal control. To assure the robustness of ML model, above analyses were repeated in amyloid ß (Aß) and apolipoprotein E (APOE) ɛ4 subgroups. We found that the accuracy of the proposed multimodal SVM method achieved 79.49% and 83.13%, respectively, in Chinese and ANDI cohorts for the diagnosis of the SCD plus individuals. Furthermore, adding Aß pathology and ApoE ɛ4 genotype information can further improve the accuracy to 85.36% and 82.52%. More importantly, the classification model exhibited the robustness in the crossracial cohorts and different subgroups, which outperforms any single and 2 modalities. The study indicates that multimodal MRI imaging combining with ML classification method yields excellent and powerful performances at categorizing SCD due to AD, suggesting potential for clinical utility.

Bi-functional NiFe2O4/SrTiO3 S-scheme heterojunction for eminent performance photocatalytic treatment of sewage effluent and electrochemical hydrazine determination.

Devising of materials that afforded dual applicability in decontamination and pollutant detection were still a towering challenge owing to the increasing flux of discharge toxic contaminants over the years. Herein, the NiFe2O4 nanoparticles-loaded on cube-like SrTiO3 (NiFe2O4/SrTiO3) composite was fabricated by a two-step hydrothermal approach providing remarkable photocatalytic treatment and electrochemical sensing of noxious pollutants in wastewater. The material traits of the fabricated composite were scrutinized by myriad characterization approaches. The NiFe2O4/SrTiO3 hybrid material demonstrated high surface area of 19.81 m2/g, adequate band gap energy of 2.75 eV, and prominent photoluminescence characteristics. In the presence of visible light, the NiFe2O4/SrTiO3 exhibited profound photocatalysis capability to eliminate sewage effluent-bearing chlortetracycline hydrochloride (CTCH) with 88.6% COD removal in 120 min, outperforming other pure materials. Meanwhile, the toxicity examination of effluent, the possible degradation pathway of CTCH and the proposed photocatalysis mechanism were also divulged. More importantly, the glassy carbon electrode was modified with synergized NiFe2O4/SrTiO3 (NiFe2O4/SrTiO3-GCE) was adopted for the precise quantification of Hydrazine (Hz). The NiFe2O4/SrTiO3-GCE obeyed first-order response for the Hz detection within the range of 1-10 mM: cyclic voltametric: limit of detection (LOD) of 0.119 µM with sensitivity of 18.9 µA µM-1 cm-2, and linear sweep voltametric: LOD of 0.222 µM with a sensitivity of 12.05 µA µM-1 cm-2. The stability and interference of modified electrode were also inspected. This work furnished valuable insights to yield a composite with the prominent S-scheme heterojunction system for quenching of charge carrier recombination and consequently contributing to the future realization into the domains of environmental clean-up and toxic chemical detection.

Controlled solvothermal synthesis of self-assembled SrTiO3 microstructures for expeditious solar-driven photocatalysis dye effluents degradation.

In this work, the self-assembled SrTiO3 (STO) microstructures were synthesized via a facile one-step solvothermal method. As the solvothermal temperature increased from 140 °C to 200 °C, the STO changed from a flower-like architecture to finally an irregularly aggregated flake-like morphology. The photocatalytic performance of as-synthesized samples was assessed through the degradation of rhodamine B (RhB) and malachite green (MG) under simulated solar irradiation. The results indicated that the photocatalytic performance of STO samples depended on their morphology, in which the hierarchical flower-like STO synthesized at 160 °C demonstrated the highest photoactivities. The photocatalytic enhancement of STO-160 was benefited from its large surface area and mesoporous configuration, hence facilitating the presence of more reactive species and accelerating the charge separation. Moreover, the real-world practicality of STO-160 photocatalysis was examined via the real printed ink wastewater-containing RhB and MG treatment. The phytotoxicity analyses demonstrated that the photocatalytically treated wastewater increased the germination of mung bean seeds, and the good reusability of synthesized STO-160 in photodegradation reaction also promoted its application in practical scenarios. This work highlights the promising potential of tailored STO microstructures for effective environmental remediation applications.

A luciferase reporter mouse model to optimize in vivo gene editing validated by lipid nanoparticle delivery of adenine base editors.

The rapid development of CRISPR genome editing technology has provided the potential to treat genetic diseases effectively and precisely. However, efficient and safe delivery of genome editors to affected tissues remains a challenge. Here, we developed luminescent ABE (LumA), a luciferase reporter mouse model containing the R387X mutation (c.A1159T) in the luciferase gene located in the Rosa26 locus of the mouse genome. This mutation eliminates luciferase activity but can be restored upon A-to-G correction by SpCas9 adenine base editors (ABEs). The LumA mouse model was validated through intravenous injection of two FDA-approved lipid nanoparticle (LNP) formulations consisting of either MC3 or ALC-0315 ionizable cationic lipids, encapsulated with ABE mRNA and LucR387X-specific guide RNA (gRNA). Whole-body bioluminescence live imaging showed consistent restoration of luminescence lasting up to 4 months in treated mice. Compared with mice carrying the wild-type luciferase gene, the ALC-0315 and MC3 LNP groups showed 83.5% ± 17.5% and 8.4% ± 4.3% restoration of luciferase activity in the liver, respectively, as measured by tissue luciferase assays. These results demonstrated successful development of a luciferase reporter mouse model that can be used to evaluate the efficacy and safety of different genome editors, LNP formulations, and tissue-specific delivery systems for optimizing genome editing therapeutics.

α-Mangostin reduces hypertension in spontaneously hypertensive rats and inhibits EMT and fibrosis in Ang II-induced HK-2 cells.

Hypertension affects a large number of individuals globally and is a common cause of nephropathy, stroke, ischaemic heart disease and other vascular diseases. While many anti-hypertensive medications are used safely and effectively in clinic practice, controlling hypertensive complications solely by reducing blood pressure (BP) can be challenging. α-Mangostin, a xanthone molecule extracted from the pericarp of Garcinia mangostana L., has shown various beneficial effects such as anti-tumor, anti-hyperuricemia, and anti-inflammatory properties. However, the effects of α-Mangostin on hypertension remain unknown. In this study, we observed that α-Mangostin significantly decreased systolic and diastolic blood pressure in spontaneously hypertensive rats (SHR), possibly through the down-regulation of angiotensin II (Ang II). We also identified early markers of hypertensive nephropathy, including urinary N-acetyl-ß-D-glucosaminidase (NAG) and ß2-microglobulin (ß2-MG), which were reduced by α-Mangostin treatment. Mechanistic studies suggested that α-Mangostin may inhibit renal tubular epithelial-to-mesenchymal transformation (EMT) by down-regulating the TGF-ß signaling pathway, thus potentially offering a new therapeutic approach for hypertension and hypertensive nephropathy.